2. Academic Validation
  3. Defining the interactome of the human mitochondrial ribosome identifies SMIM4 and TMEM223 as respiratory chain assembly factors

Defining the interactome of the human mitochondrial ribosome identifies SMIM4 and TMEM223 as respiratory chain assembly factors

  • Elife. 2021 Dec 31;10:e68213. doi: 10.7554/eLife.68213.
Sven Dennerlein # 1,  Sabine Poerschke # 1,  Silke Oeljeklaus 2 3,  Cong Wang 1,  Ricarda Richter-Dennerlein 1 4,  Johannes Sattmann 1,  Diana Bauermeister 1,  Elisa Hanitsch 1,  Stefan Stoldt 4 5 6,  Thomas Langer 7,  Stefan Jakobs 4 5 6 8,  Bettina Warscheid 2 3,  Peter Rehling 1 4 8 9
Affiliations

Affiliations

  • 1 Department of Cellular Biochemistry, University Medical Center Göttingen, Göttingen, Germany.
  • 2 Biochemistry and Functional Proteomics, Institute of Biology II, University of Freiburg, Freiburg, Germany.
  • 3 Signalling Research Centres BIOSS and CIBSS, University of Freiburg, Freiburg, Germany.
  • 4 Cluster of Excellence "Multiscale Bioimaging: from Molecular Machines to Networks of Excitable Cells" (MBExC), University of Göttingen, Göttingen, Germany.
  • 5 Department of NanoBiophotonics, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.
  • 6 Department of Neurology, University Medical Center Göttingen, Göttingen, Germany.
  • 7 Department of Mitochondrial Proteostasis, Max Planck Institute for Biology of Ageing, Cologne, Germany.
  • 8 Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Translational Neuroinflammation and Automated Microscopy, Göttingen, Germany.
  • 9 Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.
  • # Contributed equally.
PMID: 34969438 DOI: 10.7554/eLife.68213
Abstract

Human mitochondria express a genome that encodes thirteen core subunits of the oxidative phosphorylation system (OXPHOS). These proteins insert into the inner membrane co-translationally. Therefore, mitochondrial ribosomes engage with the OXA1L-insertase and membrane-associated proteins, which support membrane insertion of translation products and early assembly steps into OXPHOS complexes. To identify ribosome-associated biogenesis factors for the OXPHOS system, we purified ribosomes and associated proteins from mitochondria. We identified TMEM223 as a ribosome-associated protein involved in complex IV biogenesis. TMEM223 stimulates the translation of COX1 mRNA and is a constituent of early COX1 assembly intermediates. Moreover, we show that SMIM4 together with C12ORF73 interacts with newly synthesized cytochrome b to support initial steps of complex III biogenesis in complex with UQCC1 and UQCC2. Our analyses define the interactome of the human mitochondrial ribosome and reveal novel assembly factors for complex III and IV biogenesis that link early assembly stages to the translation machinery.

Keywords

assembly; biochemistry; cell biology; chemical biology; mitochondria; oxidative phosphorylation; ribosome; translation.

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